As a medication, it is used to treat a number of conditions incwuding anaphywaxis, cardiac arrest, and superficiaw bweeding.[1]Inhawed epinephrine may be used to improve de symptoms of croup.[10] It may awso be used for asdma when oder treatments are not effective. It is given intravenouswy, by injection into a muscwe, by inhawation, or by injection just under de skin, uh-hah-hah-hah.[1] Common side effects incwude shakiness, anxiety, and sweating. A fast heart rate and high bwood pressure may occur. Occasionawwy it may resuwt in an abnormaw heart rhydm. Whiwe de safety of its use during pregnancy and breastfeeding is uncwear, de benefits to de moder must be taken into account.[1]

A case has been made for de use of adrenawine (epinephrine) infusion in pwace of de widewy accepted treatment of inotopes for preterm infants wif cwinicaw cardiovascuwar compromise. Awdough dere is sufficient data which strongwy recommends Adrenawine infusions as a viabwe treatment, more triaws are needed in order to concwusivewy determine dat dese infusions wiww successfuwwy reduce morbidity and mortawity rates among preterm, cardiovascuwarwy compromised infants.[11]

The concept of de adrenaw meduwwa and de sympadetic nervous system being invowved in de fwight, fight and fright response was originawwy proposed by Cannon.[23] But de adrenaw meduwwa, in contrast to de adrenaw cortex, is not reqwired for survivaw. In adrenawectomized patients hemodynamic and metabowic responses to stimuwi such as hypogwycemia and exercise remain normaw.[24][25]

One physiowogicaw stimuwus to epinephrine secretion is exercise. This was first demonstrated using de denervated pupiw of a cat as an assay,[26] water confirmed using a biowogicaw assay on urine sampwes.[27] Biochemicaw medods for measuring catechowamines in pwasma were pubwished from 1950 onwards.[28] Awdough much vawuabwe work has been pubwished using fwuorimetric assays to measure totaw catechowamine concentrations, de medod is too non-specific and insensitive to accuratewy determine de very smaww qwantities of epinephrine in pwasma. The devewopment of extraction medods and enzyme-isotope derivate radio-enzymatic assays (REA) transformed de anawysis down to a sensitivity of 1 pg for epinephrine.[29] Earwy REA pwasma assays indicated dat epinephrine and totaw catechowamines rise wate in exercise, mostwy when anaerobic metabowism commences.[30][31][32]

A wink between what we now know as de sympadetic system and de wung was shown in 1887 when Grossman showed dat stimuwation of cardiac accewerator nerves reversed muscarine-induced airway constriction, uh-hah-hah-hah.[37] In experiments in de dog, where de sympadetic chain was cut at de wevew of de diaphragm, Jackson showed dat dere was no direct sympadetic innervation to de wung, but dat bronchoconstriction was reversed by rewease of epinephrine from de adrenaw meduwwa.[38] An increased incidence of asdma has not been reported for adrenawectomized patients; dose wif a predisposition to asdma wiww have some protection from airway hyper-reactivity from deir corticosteroid repwacement derapy. Exercise induces progressive airway diwation in normaw subjects dat correwates wif work woad and is not prevented by beta bwockade.[39] The progressive diwation of de airway wif increasing exercise is mediated by a progressive reduction in resting vagaw tone. Beta bwockade wif propranowow causes a rebound in airway resistance after exercise in normaw subjects over de same time course as de bronchoconstriction seen wif exercise induced asdma.[40] The reduction in airway resistance during exercise reduces de work of breading.[41]

Every emotionaw response has a behavioraw component, an autonomic component, and a hormonaw component. The hormonaw component incwudes de rewease of epinephrine, an adrenomeduwwary response dat occurs in response to stress and dat is controwwed by de sympadetic nervous system. The major emotion studied in rewation to epinephrine is fear. In an experiment, subjects who were injected wif epinephrine expressed more negative and fewer positive faciaw expressions to fear fiwms compared to a controw group. These subjects awso reported a more intense fear from de fiwms and greater mean intensity of negative memories dan controw subjects.[42] The findings from dis study demonstrate dat dere are wearned associations between negative feewings and wevews of epinephrine. Overaww, de greater amount of epinephrine is positivewy correwated wif an arousaw state of negative feewings. These findings can be an effect in part dat epinephrine ewicits physiowogicaw sympadetic responses incwuding an increased heart rate and knee shaking, which can be attributed to de feewing of fear regardwess of de actuaw wevew of fear ewicited from de video. Awdough studies have found a definite rewation between epinephrine and fear, oder emotions have not had such resuwts. In de same study, subjects did not express a greater amusement to an amusement fiwm nor greater anger to an anger fiwm.[42] Simiwar findings were awso supported in a study dat invowved rodent subjects dat eider were abwe or unabwe to produce epinephrine. Findings support de idea dat epinephrine does have a rowe in faciwitating de encoding of emotionawwy arousing events, contributing to higher wevews of arousaw due to fear.[43]

It has been found dat adrenergic hormones, such as epinephrine, can produce retrograde enhancement of wong-term memory in humans. The rewease of epinephrine due to emotionawwy stressfuw events, which is endogenous epinephrine, can moduwate memory consowidation of de events, ensuring memory strengf dat is proportionaw to memory importance. Post-wearning epinephrine activity awso interacts wif de degree of arousaw associated wif de initiaw coding.[44] There is evidence dat suggests epinephrine does have a rowe in wong-term stress adaptation and emotionaw memory encoding specificawwy. Epinephrine may awso pway a rowe in ewevating arousaw and fear memory under particuwar padowogicaw conditions incwuding post-traumatic stress disorder.[43] Overaww, "Extensive evidence indicates dat epinephrine (EPI) moduwates memory consowidation for emotionawwy arousing tasks in animaws and human subjects.”[45]
Studies have awso found dat recognition memory invowving epinephrine depends on a mechanism dat depends on β adrenoceptors.[45] Epinephrine does not readiwy cross de bwood–brain barrier, so its effects on memory consowidation are at weast partwy initiated by β adrenoceptors in de periphery. Studies have found dat sotawow, a β adrenoceptor antagonist dat awso does not readiwy enter de brain, bwocks de enhancing effects of peripherawwy administered epinephrine on memory.[46] These findings suggest dat β adrenoceptors are necessary for epinephrine to have an effect on memory consowidation, uh-hah-hah-hah.

For noradrenawine to be acted upon by PNMT in de cytosow, it must first be shipped out of granuwes of de chromaffin cewws. This may occur via de catechowamine-H+ exchanger VMAT1. VMAT1 is awso responsibwe for transporting newwy syndesized adrenawine from de cytosow back into chromaffin granuwes in preparation for rewease.[47]

Increased epinephrine secretion is observed in pheochromocytoma, hypogwycemia, myocardiaw infarction and to a wesser degree in benign essentiaw famiwiaw tremor. A generaw increase in sympadetic neuraw activity is usuawwy accompanied by increased adrenawine secretion, but dere is sewectivity during hypoxia and hypogwycaemia, when de ratio of adrenawine to noradrenawine is considerabwy increased.[48][49][50] Therefore, dere must be some autonomy of de adrenaw meduwwa from de rest of de sympadetic system

Myocardiaw infarction is associated wif high wevews of circuwating epinephrine and norepinephrine, particuwarwy in cardiogenic shock.[51][52]

Benign famiwiaw tremor (BFT) is responsive to peripheraw β adrenergic bwockers and β2-stimuwation is known to cause tremor. Patients wif BFT were found to have increased pwasma epinephrine, but not norepinephrine.[53][54]

Low, or absent, concentrations of epinephrine can be seen in autonomic neuropady or fowwowing adrenawectomy. Faiwure of de adrenaw cortex, as wif Addisons disease, can suppress epinephrine secretion as de activity of de syndesing enzyme, phenywedanowamine-N-medywtransferase, depends on de high concentration of cortisow dat drains from de cortex to de meduwwa.[55][56][57]

However, de pharmacowogist John Abew had awready prepared an extract from adrenaw gwands as earwy as 1897, and coined de name epinephrine to describe it (from de Greek epi and nephros, "on top of de kidneys")[58]. In de bewief dat Abew's extract was de same as Takamine's (a bewief since disputed), epinephrine became[when?] de generic name in de US[58], and remains de pharmaceuticaw'sUnited States Adopted Name and Internationaw Nonproprietary Name (dough de name adrenawine is freqwentwy used).

The terminowogy is now one of de few differences between de INN and BAN systems of names.[59] Awdough European heawf professionaws and scientists preferentiawwy use de term adrenawine, de converse is true among American heawf professionaws and scientists. Neverdewess, even among de watter, receptors for dis substance are cawwed adrenergic receptors or adrenoceptors, and pharmaceuticaws dat mimic its effects are often cawwed adrenergics.

As a hormone, epinephrine acts on nearwy aww body tissues. Its actions vary by tissue type and tissue expression of adrenergic receptors. For exampwe, high wevews of epinephrine causes smoof muscwe rewaxation in de airways but causes contraction of de smoof muscwe dat wines most arteriowes.

Its actions are to increase peripheraw resistance via α1 receptor-dependent vasoconstriction and to increase cardiac output via its binding to β1 receptors. The goaw of reducing peripheraw circuwation is to increase coronary and cerebraw perfusion pressures and derefore increase oxygen exchange at de cewwuwar wevew.[64] Whiwe epinephrine does increase aortic, cerebraw, and carotid circuwation pressure, it wowers carotid bwood fwow and end-tidaw CO2 or ETCO2 wevews. It appears dat epinephrine may be improving macrocircuwation at de expense of de capiwwary beds where actuaw perfusion is taking pwace.[65]

Epinephrine may be qwantified in bwood, pwasma or serum as a diagnostic aid, to monitor derapeutic administration, or to identify de causative agent in a potentiaw poisoning victim. Endogenous pwasma epinephrine concentrations in resting aduwts are normawwy wess dan 10 ng/L, but may increase by 10-fowd during exercise and by 50-fowd or more during times of stress. Pheochromocytoma patients often have pwasma adrenawine wevews of 1000–10,000 ng/L. Parenteraw administration of epinephrine to acute-care cardiac patients can produce pwasma concentrations of 10,000 to 100,000 ng/L.[66][67]

The major physiowogic triggers of adrenawine rewease center upon stresses, such as physicaw dreat, excitement, noise, bright wights, and high or wow ambient temperature. Aww of dese stimuwi are processed in de centraw nervous system.[74]

Extracts of de adrenaw gwand were first obtained by Powish physiowogist Napoweon Cybuwski in 1895. These extracts, which he cawwed nadnerczyna ("adrenawin"), contained adrenawine and oder catechowamines.[76] American ophdawmowogist Wiwwiam H. Bates discovered adrenawine's usage for eye surgeries prior to 20 Apriw 1896.[77] Japanese chemist Jokichi Takamine and his assistant Keizo Uenaka independentwy discovered adrenawine in 1900.[78][79] In 1901, Takamine successfuwwy isowated and purified de hormone from de adrenaw gwands of sheep and oxen, uh-hah-hah-hah.[80] Adrenawine was first syndesized in de waboratory by Friedrich Stowz and Henry Drysdawe Dakin, independentwy, in 1904.[79]

An adrenawine junkie is somebody who engages in sensation-seeking behavior drough "de pursuit of novew and intense experiences widout regard for physicaw, sociaw, wegaw or financiaw risk".[81] Such activities incwude extreme and risky sports, substance abuse, unsafe sex, and crime. The term rewates to de increase in circuwating wevews of adrenawine during physiowogicaw stress.[82] Such an increase in de circuwating concentration of adrenawine is secondary to activation of de sympadetic nerves innervating de adrenaw meduwwa, as it is rapid and not present in animaws where de adrenaw gwand has been removed.[83] Awdough such stress triggers adrenawine rewease, it awso activates many oder responses widin de centraw nervous system reward system which drives behavioraw responses, so whiwe de circuwating adrenawine concentration is present, it may not drive behavior. Neverdewess, adrenawine infusion awone does increase awertness[84] and has rowes in de brain incwuding de augmentation of memory consowidation, uh-hah-hah-hah.[82]:147–8

Adrenawine has been impwicated in feats of great strengf, often occurring in times of crisis. For exampwe, dere are stories of a parent wifting part of a car when deir chiwd is trapped underneaf.[85][86]